How medicinal chemists learned about log P
- 17 July 2018
- journal article
- research article
- Published by Springer Nature in Journal of Computer-Aided Molecular Design
- Vol. 32 (8) , 809-819
Abstract
Although log P is now recognized to be a key factor that determines the bioactivity of a molecule, the focus of medicinal chemists on hydrophobicity and log P started with the quantitative structure–activity relationships (QSAR) publications of Hansch and Fujita. Their original publication represents a dramatic change of focus to incorporate consideration of log P after a decade of work unsuccessfully attempting to use the Hammett equation to explain the structure-activity relationships of plant growth regulators. QSAR allows one to explore the quantitative relationship between log P and biological activity even when other factors also influence potency. In particular, Hansch’s publications of thousands of QSAR equations demonstrate that a relationship of biological activity with log P is indeed a general phenomenon. Hansch’s group also provided data and tools that enable others to explore the relationship between log P and the biological activity of compounds of interest.Keywords
This publication has 96 references indexed in Scilit:
- Interfaces and the driving force of hydrophobic assemblyNature, 2005
- Structure of medicinal chemistryJournal of Medicinal Chemistry, 1976
- Electronic Structure and Plant Growth Activity of Substituted 1-Naphthoic Acid Derivatives1,2Journal of the American Chemical Society, 1960
- Electronic Structure and Auxin Activity of Benzoic Acid DerivativesJournal of the American Chemical Society, 1958
- The Evaluation of Inductive and Resonance Effects on Reactivity. I. Hydrolysis Rates of Acetals of Non-conjugated Aldehydes and Ketones1aJournal of the American Chemical Society, 1955
- Polar and Steric Substituent Constants for Aliphatic and o-Benzoate Groups from Rates of Esterification and Hydrolysis of Esters1Journal of the American Chemical Society, 1952
- Naphthoquinone Antimalarials. XV. Distribution between Organic Solvents and Aqueous Buffers1,2Journal of the American Chemical Society, 1948
- Naphthoquinone Antimalarials. I. General Survey1,2Journal of the American Chemical Society, 1948
- The Structure and Entropy of Ice and of Other Crystals with Some Randomness of Atomic ArrangementJournal of the American Chemical Society, 1935
- V.—On the Connection between Chemical Constitution and Physiological Action. Part. I.—On the Physiological Action of the Salts of the Ammonium Bases, derived from Strychnia, Brucia, Thebaia, Codeia, Morphia, and NicotiaTransactions of the Royal Society of Edinburgh, 1868